To link to the entire object, paste this link in email, IM or documentTo embed the entire object, paste this HTML in websiteTo link to this page, paste this link in email, IM or documentTo embed this page, paste this HTML in website

MODULATION OF T CELL RESPONSES BY
EXTRACELLULAR NUCLEOTIDES
by
Fred Jullien Aswad
A Dissertation Presented to the
FACULTY OF THE GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
DOCTOR OF PHILOSOPHY
(MOLECULAR MICROBIOLOGY AND IMMUNOLOGY)
December 2006
Copyright 2006 Fred Jullien Aswad

Modulation of immune responses involves a complex set of signaling molecules and pathways. Purine nucleotides such as nicotinamide adenine dinucleotide (NAD) and adenosine triphosphate (ATP) have been demonstrated to regulate cells of the adaptive and immune system. Aside from basic demonstrations however, much of how purine nucleotides modulate T cells has remained unknown. This project set out to better understand how NAD and ATP modulate T cells in vitro and in vivo. In this report, purinergic receptor P2X7 (P2X7R) is identified as mediating the effects of NAD and ATP. Moreover, signaling through P2X7R can result in T cell death or activation depending on the particular condition. Differences in sensitivity to P2X7R signaling are demonstrated, and a correlation with cell surface P2X7R expression is shown. In support of the in vitro data presented, using a model of liver injury and contact hypersensitivity, the effects of purinergic receptor signaling on T cells in vivo is demonstrated. The work presented here provides evidence that purinergic signaling through the P2X7R is an important immunomodulatory mechanism and a potentially important therapeutic target.

MODULATION OF T CELL RESPONSES BY
EXTRACELLULAR NUCLEOTIDES
by
Fred Jullien Aswad
A Dissertation Presented to the
FACULTY OF THE GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
DOCTOR OF PHILOSOPHY
(MOLECULAR MICROBIOLOGY AND IMMUNOLOGY)
December 2006
Copyright 2006 Fred Jullien Aswad